Objectives To determine whether birth weight and adult body size interact to predict coronary heart disease in women, as has been observed for men. To determine whether birth weight and adult body size interact to predict risk of stroke. Design Longitudinal cohort study. Setting and participants 66 111 female nurses followed since 1976 who were born of singleton, term pregnancies and reported their birth weight in 1992. Main outcome measures 1504 events of coronary heart disease (myocardial infarction or sudden cardiac death) and 1164 strokes. Results For each kilogram of higher birth weight, age adjusted hazard ratios from prospective analysis were 0.77 (95% confidence interval 0.69 to 0.87) for coronary heart disease and 0.89 (0.78 to 1.01) for total stroke. In combined prospective and retrospective analysis, hazard ratios were 0.84 (0.76 to 0.93) for total stroke, 0.83 (0.71 to 0.96) for ischaemic stroke, and 0.86 (0.66 to 1.11) for haemorrhagic stroke. Exclusion of macrosomic infants (> 4536 g) yielded stronger estimates. Risk of coronary heart disease was especially high for women who crossed from a low centile of weight at birth to a high centile of body mass index in adulthood. The association of lower birth weight with increased risk of stroke was apparent across categories of body mass index in adults and was not especially strong among heavier women. Conclusions Higher body mass index in adulthood is an especially strong risk factor for coronary heart disease among women who were small at birth. In this large cohort of women, size at birth and adiposity in adulthood interacted to predict events of coronary heart disease but not stroke events.